Secondary and tertiary structure are important to the function of many naturally occurring RNAs. In this proposal we plan to use a number of different approaches to investigate RNA structure in solution including high resolution NMR (transient nuclear Overhauser effect, spin-lattice and spin-spin relaxation measurements), photochemical mapping of secondary structure, along with other spectroscopic methods (ESR, fluorescence spectra and lifetime measurements, hypochromism, Fourier transform infrared). The molecules of interest include tRNA, 5S RNA, messenger RJA and simple sequence synthetic RNA. The tRNA related problems of interest include nature of, and factors responsible for the strong metal ion binding sites of tRNA, environmental effects on tRNA structure, functional role of non-Watson-Crick base pairs and the nature of tRNA drug binding sites. The simple sequence RNA will be examined using a variety of pulsed NMR techniques with the ultimate goal of examining not only the hydrogen bonding schemes which exist between non-Watson-Crick base pairs, but of determining the precise structure of these molecules in solution. In other studies we shall examine the molecular mechanism by which small molecules (amino acids, oligopeptides, drugs) recognize various RNA molecules. These studies are of interest because the molecules chosen for study are biologically important, their functions are affected by their secondary and tertiary structure and novel methods are proposed to investigate the secondary and tertiary structure of RNAs in solution.